The pathophysiology of acute, persistent and reactivation infection with varicella zoster virus (VZV) is poorly defined. Studies of VZV infection have been hampered by the lack of a suitable animal model of VZV infections. The cultivation of VZV in tissue cultures derived from the fetal guinea pig suggested that it might be possible to adapt VZV to guinea pigs. We have demonstrated that guinea pigs exposed to fetal guinea pig tissue culture-adapted VZV developed nasopharyngeal viral replication, viremia, and the production of specific humoral antibody. Airborne transmission of VZV to cagemates has also been observed. In the research outlined in this application, it is proposed to explore the guinea pig as a model of acute, persistent and recurrent VZV infection. We will examine adaptation of the virus to the guinea pig. We will characterize the acute infection in normal and immunologically modified guinea pigs and we will explore specific immunologic responses of the guinea pig to VZV infection. In addition, we will continue to expand our clinical observations of the viremia associated with varicella and herpes zoster in humans.